This application is to continue as a participant in the collaborative multicenter prospective natural history of perinatal HIV-1 infection, the Women and Infants Transmission Study (WITS) now in the antiretroviral treatment era. The objectives of the study continue to be 1) the understanding of determinants of mother to infant HIV-1 transmission, 2) the natural history and determinants of disease progression in pediatric HIV-1 infection and 3) the effect of pregnancy on the natural history of HIV-1 infection in women. Specific objectives of WITS 3, as this initiative is called, include 1) determining mechanisms of perinatal HIV transmission and maternal cofactors related to transmission including the role of maternal drug use, the role of the placenta, the role and characteristics of HIV in the birth canal, and of maternal coinfections; 2) evaluation of factors related to successful perinatal HIV prevention strategies, with intense assessment of transmission cases that occur despite perinatal use of antiretroviral therapy; 3) determination of the impact of pregnancy on disease progression of HIV infection among women through the postpartum period, including immunologic and virologic changes in pregnant HIV-infected women who receive antiretroviral therapy during pregnancy; 4) characterization of acute HIV infection among HIV infected infants and children in light of antiretroviral, prophylactic and immune-based therapy and 5) determination of factors predicting pediatric disease progression among the cohort of HIV infected children in WITS. To this end the study will enroll annually between 30 and 40 HIV-1 infected pregnant women who agree to be followed in this history study. Information is collected on behaviors, drug use, general health, immunologic status, HIV stage of disease, HIV phenotype, HIV quantitative culture as measured bycellar infectious units per million, plasma RNA copy number, a host of lymphocyte phenotypes by flow cytometry, genital cultures including cervical lavage for HIV studies, placentas, products of conception, pediatric HIV disease status, growth and neurodevelopment. A repository of PBMC that are frozen for viability as well as of plasma is collected at every study visit for to empower the study to examine old questions with newly developed technologies as well as new scientific questions that emerge from the advancing areas of HIV basic research. The HIV infected women are followed indefinitely as are the infected children and a subset of the exposed and uninfected children. This site places particular emphasis on the understanding of the influence of hard drug use on maternal-infant HIV transmission and on pediatric disease progression that have been noted in the WITS. Characteristics of the viral phenotypes and the immune response in hard drug users compared to nondrug will be examined to better understand the mechanisms(s) for these associations and their implications for HIV-1 pathogenesis in general. Studies of compliance to perinatal transmission prevention strategies in drug using nondrug using populations as well as the examination of alternate means of ascertaining hard drug usage are also being spearheaded by this site.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01AI034842-05
Application #
2672257
Study Section
Special Emphasis Panel (ZAI1-MSQ-A (M1))
Project Start
1994-09-01
Project End
2001-08-31
Budget Start
1998-09-01
Budget End
1999-08-31
Support Year
5
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Columbia University (N.Y.)
Department
Pediatrics
Type
Schools of Medicine
DUNS #
167204994
City
New York
State
NY
Country
United States
Zip Code
10032
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Bauer, Greta R; Colgrove, Robert C; Larussa, Philip S et al. (2006) Antiretroviral resistance in viral isolates from HIV-1-transmitting mothers and their infants. AIDS 20:1707-12
Colgrove, Robert C; Millet, Amy; Bauer, Greta R et al. (2005) Gag-p6 Tsg101 binding site duplications in maternal-infant HIV infection. AIDS Res Hum Retroviruses 21:191-9
LaMonte, Ashley C; Paul, Mary E; Read, Jennifer S et al. (2004) Persistent parvovirus B19 infection without the development of chronic anemia in HIV-infected and -uninfected children: the Women and Infants Transmission Study. J Infect Dis 189:847-51
Ioannidis, John P A; Tatsioni, Athina; Abrams, Elaine J et al. (2004) Maternal viral load and rate of disease progression among vertically HIV-1-infected children: an international meta-analysis. AIDS 18:99-108
Llorente, Antolin; Brouwers, Pim; Charurat, Manhattan et al. (2003) Early neurodevelopmental markers predictive of mortality in infants infected with HIV-1. Dev Med Child Neurol 45:76-84
Tuomala, Ruth E; Shapiro, David E; Mofenson, Lynne M et al. (2002) Antiretroviral therapy during pregnancy and the risk of an adverse outcome. N Engl J Med 346:1863-70
LaRussa, Philip; Magder, Laurence S; Pitt, Jane et al. (2002) Association of HIV-1 viral phenotype in the MT-2 assay with perinatal HIV transmission. J Acquir Immune Defic Syndr 30:88-94
Read, J S; Tuomala, R; Kpamegan, E et al. (2001) Mode of delivery and postpartum morbidity among HIV-infected women: the women and infants transmission study. J Acquir Immune Defic Syndr 26:236-45
Macmillan, C; Magder, L S; Brouwers, P et al. (2001) Head growth and neurodevelopment of infants born to HIV-1-infected drug-using women. Neurology 57:1402-11

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